MicroRNA-497 inhibits tumor growth and increases chemosensitivity to 5-fluorouracil treatment by targeting KSR1
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Lin Wang1,*, Cheng-fei Jiang1,*, Dong-mei Li1,3,*, Xin Ge1, Zhu-mei Shi1,4, Chong-yong Li1, Xue Liu1, Yu Yin1,5, Linlin Zhen2, Ling-Zhi Liu6, Bing-Hua Jiang1,6
1State Key Lab of Reproductive Medicine, Collaborative Innovation Center for Cancer Personalized Medicine, Department of Pathology, Nanjing Medical University, Nanjing, China
2Department of Breast and Thyroid Surgery, Huai’an First People's Hospital, Huai’an, Jiangsu, China
3Ninggao Personalized Medicine and Technology Innovation Center, Nanjing, China
4Department of Neurosurgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
5Department of Pathology, Anhui Medical University, Hefei, China
6Department of Pathology, Anatomy and Cell Biology, Thomas Jefferson University, Philadelphia, PA, USA
*These authors have contributed equally to this work
Bing-Hua Jiang, e-mail: firstname.lastname@example.org
Linlin Zhen, e-mail: email@example.com
Keywords: miR-497, colorectal cancer, KSR1, tumorigenesis, chemosensitivity
Received: July 28, 2015 Accepted: November 16, 2015 Published: December 09, 2015
Colorectal cancer (CRC) is one of the leading cancer-related causes of death in the world. Recently, downregulation of microRNA-497 (miR-497) has been observed in CRC tissues. In this study, we found that miR-497 expression levels were downregulated in human CRC specimens compared to the adjacent normal tissues. MiR-497 expression levels were strongly correlated with clinical stages and lymph node metastases. Furthermore, kinase suppressor of ras 1 (KSR1), a known oncogene, was a direct target of miR-497, and KSR1 expression levels were inversely correlated with miR-497 expression levels in human CRC specimens. Overexpression of miR-497 inhibited cell proliferation, migration, invasion and increased chemosensitivity to 5-fluorouracil treatment, whereas forced expression of KSR1 had the opposite effect. Taken together, these results revealed that lower miR-497 levels in human CRC tissues induce KSR1 expression which is associated with CRC cancer occurrence, advanced stages, metastasis and chemoresistance. Lower miR-497 levels may be a potential biomarker for CRC advanced stages and treatment response.
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